Radiation therapy (RT)-free pembrolizumab plus chemotherapy (P+C) for PD-L1 TPS ≥50% locally advanced non-small cell lung cancer (LA-NSCLC): An early report analyzing depth of response from multicenter single arm phase II study (Evolution trial: WJOG11819L).
Authors: Akito Hata, Taira Ninomaru, Hideaki Okada, Yoshihito Kogure, Masahide Oki, Nobuyuki Katakami, Takashi Kijima, Toshihide Yokoyama, Hirotaka Matsumoto, Yuki Sato, Terufumi Kato, Shunichi Sugawara, Takeshi Sawada, Kenichi Yoshimura, Takashi Seto, Nobuyuki Yamamoto, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2023)

8544 Background: Standard of care for unresectable LA-NSCLC is chemoradiation therapy (CRT) followed by durvalumab (D). Survival curves of P monotherapy/P+C for PD-L1 TPS ≥50% stage IV NSCLC suggested possible comparable survival to CRT for stage III patients (pts). Moreover, some studies of neoadjuvant C+immunotherapy (I) for stage III pts have demonstrated high pCR and MPR rates, implying potentially outstanding efficacy of C+I for earlier stage. We thus hypothesized P+C without RT in PD-L1 ≥50% LA-NSCLC pts provides a comparable efficacy to CRT followed by D while avoiding CRT-induced severe toxicities. Methods: This early report focuses on depth of response in a phase II study by WJOG. P with platinum plus pemetrexed (PEM) (non-squamous) or P with carboplatin plus nab-paclitaxel (squamous) was administered every 3 weeks without RT. After four cycles of induction P+C, P with PEM (non-squamous) or P alone (squamous) was continued until progression or 2 years. The primary endpoint was PFS rate at 2 years. Results: Between May 2020 and February 2022, 21 pts were enrolled. Median age was 74 (range, 53-89). Stage IIIA/B/C included 12 (57%)/6 (29%)/3 (14%), respectively. Histologic subtypes were 13 (62%) adeno, 5 (24%) squamous, and 3 (14%) others. Investigator-assessed best response: 8 (38%) CR; 10 (48%) PR; 2 (10%) SD; and 1 (5%) NE were confirmed, resulting in response rate (RR) of 86% and disease control rate of 95%. RR of TPS 50-79% and 80-100% were 78% and 92%, respectively. Deep response (DR): defined as tumor shrinkage ≥80% was obtained in 12 (57%) of 21 pts. DR was accomplished in 4 (44%) of 9 TPS 50-79% and 8 (67%) of 12 TPS 80-100%. Median time to response was 43 (range, 41-92) days. Early tumor shrinkage (ETS): PR-in at the time of first CT evaluation (6 weeks) was achieved in 16 (89%) of 18 CR+PR pts. At the time of data cut-off, median follow-up period was 18.5 (range, 0.3-29.0) months, and 14 (67%) of 21 pts were progression-free. All 12 pts achieving DR, including all 8 CR were progression-free, also in 14 (88%) of 16 ETS pts. Three pts after local progression received salvage definitive-CRT. Median number of P administrations was 20 (range, 1-35). AEs ≥grade 3 were observed in 11 (52%) pts, including: 2 (10%) pneumonitis; 2 (10%) pneumonia; 1 (5%) diarrhea; 1 (5%) ALT elevation; and 1 (5%) acute heart failure, excluding hematological AEs. There was one (5%) possible grade 5 AE (pneumonia). Conclusions: RT-free P+C exerted a notably high RR, including some CRs. The deeper/earlier response and higher PD-L1 TPS could be associated with the higher progression-free incidence at the data cut-off. To investigate our hypothesis: RT-free P+C can be a less toxic curative option in selected LA-NSCLC pts with PD-L1 TPS ≥50%, further matured data is warranted. Clinical trial information: NCT04153734 .